Sublethal Trauma Model With Systemic Endotoxemia for the Study of Microcirculatory Disorders After the Second Hit

Background Experimental models often cannot simulate the clinical situation in traumatized patients where the septic second hit finally leads to multiple organ dysfunction syndrome and death. We present an experimental animal model combining initial standardized soft tissue trauma to the left hindli...

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Bibliographic Details
Published in:The Journal of surgical research 2008-06, Vol.147 (1), p.68-74
Main Authors: Gierer, Philip, M.D, Hoffmann, Johannes N., M.D, Mahr, Felix, Menger, Michael D., M.D, Mittlmeier, Thomas, M.D, Gradl, Georg, M.D, Vollmar, Brigitte, M.D
Format: Article
Language:English
Subjects:
Animals
apoptosis
Biological and medical sciences
Blood Coagulation Disorders - etiology
coagulation disorder
Disease Models, Animal
endotoxemia
Endotoxemia - physiopathology
General aspects
Hematologic and hematopoietic diseases
Hemodynamics
inflammation
intravital fluorescence microscopy
Lipopolysaccharides - toxicity
Male
Medical sciences
Microcirculation
Microscopy, Fluorescence
Muscle, Skeletal - blood supply
perfusion failure
Platelet diseases and coagulopathies
Rats
Rats, Sprague-Dawley
Soft Tissue Injuries - complications
Soft Tissue Injuries - physiopathology
soft tissue trauma
Surgery
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Summary:Background Experimental models often cannot simulate the clinical situation in traumatized patients where the septic second hit finally leads to multiple organ dysfunction syndrome and death. We present an experimental animal model combining initial standardized soft tissue trauma to the left hindlimb of rats with subsequent sublethal systemic endotoxemia. Materials and methods This study characterizes the influence of trauma and systemic endotoxemia on nutritive blood flow, inflammatory cell-cell interaction and tissue cell integrity in the traumatized region. Results At 24 h after local tissue contusion, in vivo analysis of the skeletal muscle microcirculation by means of high resolution fluorescence microscopy revealed intravascular leukocyte accumulation and impairment of nutritive perfusion with tissue hypoxia. Moreover, muscle tissue damage was characterized by myocyte cell apoptosis. Additional systemic exposure of animals to E. coli lipopolysaccharide at 6 h after soft tissue contusion caused a drop in arterial blood pressure as well as coagulatory disorders, as given by marked thrombocytopenia and reduced thromboplastin times. In double-hit exposed animals, skeletal muscle microcirculation presented with an aggravation of inflammation, perfusion failure, and apoptotic cell death after 24 h. Conclusions This model more closely resembles the scenario of polytraumatized patients with the risk of secondary infections and, thus, is suited to characterize anti-inflammatory drugs with respect to their potential to interfere with microcirculatory disorders and elaboration of disseminated intravascular coagulation after trauma.
ISSN:0022-4804
1095-8673
DOI:10.1016/j.jss.2007.07.025